The production of parathyroid hormone-related protein (PTHrP) has been identified in the lactating mammary gland of many species. The normal physiologic function of PTHrP produced by the mammary gland is not clearly understood. Evidence to date supports multiple functions for PTHrP acting locally within the normal mammary gland including: 1) paracrine/autocrine regulation of mammary gland differentiation, 2) regulation of calcium transport into the milk, 3) regulation of myoepithelial relaxation and 4) regulation of regional blood flow. Further progress in understanding the normal physiologic function of PTHrP in the mammary gland will be facilitated by using in vitro models that distinguish the contribution of individual mammary cell subtypes and their interactions. The use of separate populations of rat mammary alveolar epithelial and myoepithelial cells, as well as mouse mammary cell lines which produce PTHrP in vitro, will permit investigations of the cell-specific regulation of both PTHrP and the mammary PTH/PTHrP receptor. The proposed research is designed to test the OVERALL HYPOTHESIS that PTHrP produced locally within the mammary gland functions through specific membrane receptors on alveolar epithelial and myoepithelial cells to maintain the functional differentiation of alveolar epithelium.